TRIM65-catalized Ubiquitination is Essential for MDA5-mediated Antiviral Innate Immunity

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2016 Dec 30

PMID 28031478

Citations 91

Authors

Xueting Lang

Tiantian Tang

Tengchuan Jin

Chen Ding

Rongbin Zhou

Wei Jiang

Affiliations

Soon will be listed here.

Abstract

MDA5 plays a critical role in antiviral innate immunity by functioning as a cytoplasmic double-stranded RNA sensor that can activate type I interferon signaling pathways, but the mechanism for the activation of MDA5 is poorly understood. Here, we show that TRIM65 specifically interacts with MDA5 and promotes K63-linked ubiquitination of MDA5 at lysine 743, which is critical for MDA5 oligomerization and activation. Trim65 deficiency abolishes MDA5 agonist or encephalomyocarditis virus (EMCV)-induced interferon regulatory factor 3 (IRF3) activation and type I interferon production but has no effect on retinoic acid-inducible I (RIG-I), Toll-like receptor 3 (TLR3), or cyclic GMP-AMP synthase signaling pathways. Importantly, Trim65 mice are more susceptible to EMCV infection than controls and cannot produce type I interferon in vivo. Collectively, our results identify TRIM65 as an essential component for the MDA5 signaling pathway and provide physiological evidence showing that ubiquitination is important for MDA5 oligomerization and activation.

Citing Articles

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